mAbs最新文献

{"title":"Achieving Acceleration to First-in-Human: MSD's Learnings on Platform Method Validation Strategy.","authors":"Xiaoqing Hua, Jorge Quiroz, Joop Waterval, Brian Harrison, Maria DeBruin, Lynn Gennaro","doi":"10.1080/19420862.2025.2468840","DOIUrl":"10.1080/19420862.2025.2468840","url":null,"abstract":"<p><p>Over the past decades, the number of therapeutic protein pipelines in early-phase clinical studies has increased dramatically. The rapid growth in the pipeline underscores the need to accelerate early-stage development and enable fast first-in-human (FIH) trials to bring novel therapies to patients. Across the industry, various efforts have been developed to achieve this goal. In this communication, a platform analytical method validation approach developed and used by MSD for FIH programs is described. A case study from the release panel, a polysorbate 80 (PS-80) platform method is utilized to illustrate the workflow. In this approach, historical validation data within the same modality are summarized and supplemented with statistical analyses to justify a limited validation for future pipeline projects. The platform method validation strategy has reduced the overall validation timeline from up to 4 months to 1-2 months and has successfully been implemented in FIH filings. This communication provides insights to pharmaceutical companies interested in developing platform analytical method validation approaches for fast FIH studies.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2468840"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying antibody binding: techniques and therapeutic implications.","authors":"James Lodge, Lewis Kajtar, Rachel Duxbury, David Hall, Glenn A Burley, Joanna Cordy, James W T Yates, Zahra Rattray","doi":"10.1080/19420862.2025.2459795","DOIUrl":"10.1080/19420862.2025.2459795","url":null,"abstract":"<p><p>The binding kinetics of an antibody for its target antigen represent key determinants of its biological function and success as a novel biotherapeutic. Defining these interactions and kinetics is critical for understanding the pharmacological and pharmacodynamic profiles of antibodies in therapeutic applications, with line of sight to clinical translation. In this review, we discuss the latest developments in approaches to measure and modulate antibody-antigen interactions, including antibody engineering, novel antibody formats, current, and emerging technologies for measuring antibody-antigen binding interactions, and emerging perspectives within the field. We also explore how emerging computational methods are set to become powerful tools for modeling antibody-binding interactions under physiologically relevant conditions. Finally, we consider the therapeutic implications of modulating target engagement in terms of pharmacodynamics and pharmacokinetics.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2459795"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production.","authors":"Heather J Bax, Jitesh Chauhan, Alexandra J McCraw, Melanie Grandits, Chara Stavraka, Heike Lentfer, Tim Hillyer, Simon Carroll, Kim Vigor, Chris Selkirk, Mariangela Figini, Jack Cheeseman, Paulina A Urbanowicz, Richard A Gardner, Daniel I R Spencer, Nigel Westwood, Sarah Mellor, James Spicer, Debra H Josephs, Sophia N Karagiannis","doi":"10.1080/19420862.2025.2451295","DOIUrl":"10.1080/19420862.2025.2451295","url":null,"abstract":"<p><p>Antibodies used for cancer therapy are monoclonal IgGs, but tumor-targeting IgE antibodies have shown enhanced effector cell potency against cancer in preclinical models. Research-grade recombinant IgE antibodies have been generated and studied for several decades. The recent Phase 1 clinical trial of the first-in-class MOv18 IgE, however, necessitated the inaugural process development and scaled manufacture of a recombinant IgE to clinical quality standards. During the process development and scaled Good Manufacturing Practice production, we demonstrate the retention of glycosylation state, biophysical profile, and functional characteristics of MOv18 IgE, including Fc-mediated mast cell degranulation and tumor cell killing. Assessment of manufacturing parameters shows expected pH, purity, concentration, and stability properties, as well as below threshold levels of known biological manufacturing contaminants. We confirm the suitability of the pipeline described for generating intact, functionally active, clinical-grade material for this novel therapeutic class as an Investigational Medicinal Product (IMP), with comparable characteristics to the original research-grade antibody. Furthermore, we screened patient blood <i>ex vivo</i> for potential type I hypersensitivity reaction to MOv18 IgE, using the basophil activation test, to identify patients not predicted to be hypersensitive to MOv18 IgE administration. This study supports the production of functionally active clinical grade (IMP) recombinant IgE and paves the way for the development of a new therapeutic antibody class for a range of antigenic specificities and disease settings.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2451295"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing asymmetric antibody purification: a semi-automated process and its digital integration.","authors":"Christophe Prince, Despoina Georgiadou, Manuela Machatti, Matthias Hermann, Erwin van Puijenbroek","doi":"10.1080/19420862.2025.2467388","DOIUrl":"10.1080/19420862.2025.2467388","url":null,"abstract":"<p><p>Over the past decades, immunization and display technologies have considerably increased the potential for generating new binders against cell surface targets. Concomitantly, the complexity of biologic therapeutic drugs has also increased, with new asymmetric formats such as bispecific antibodies or antibody fusion proteins making the supply of molecules for preclinical drug discovery more challenging. The purification of those molecules is crucial, and an efficient purification platform for drug discovery research units should have multiple aims. First, it needs to deliver the highest quality proteins for research activities at a fast pace in order to increase screening capacities. Second, it has to deliver protein with sufficient yield in order to cover the project requirements and minimize the repetition of production cycles. Through a case study for a bispecific antibody, we describe a semi-automated and digitalized purification platform aiming at accelerating and optimizing the supply of asymmetric antibodies for drug discovery. We show how the automation of repetitive tasks and the digitalization of the process can lead to increased throughput in the context of complex purifications, including a cation exchange chromatography separation step. Furthermore, we highlight how process digitalization leads to enhanced data capture and accessibility, facilitating decision-making along the purification process. With a maximal throughput of 36 asymmetric antibodies per week and data proving the consistency of the quality delivered, this platform represents a step forward in the supply of complex antibody formats for preclinical drug discovery.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2467388"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings of the 15^th European immunogenicity platform open symposium on immunogenicity of biopharmaceuticals.","authors":"Sophie Tourdot, Karien Bloem, Lysie Champion, Anne S De Groot, Axel Ducret, Patrick Garidel, Joanna Grudzinska-Goebel, Michael Gutknecht, Timothy Hickling, Frank Horling, Marina Ichetovkin, Alison Johnson, Issa Jyamubandi, Anette Karle, Arno Kromminga, Ebru Aydin Kurtulmus, Floris Loeff, Bernard Maillere, Lydia Michaut, Francesca Minelli, Morten Nielsen, Vivek Nayak, Robert Nelson, Marc Pallardy, Sofie Pattyn, Joao Pedras-Vasconelos, Elise Pepermans, Alain Poyau, Matthias Reichel, Amy Rosenberg, Zuben Sauna, Manisha Saxena, Noel Smith, Veerle Snoeck, Lester Thoo, Michael Tovey, Daniela Verthelyi, Rene Wuttke, Daniel Yerly, Daniel Kramer","doi":"10.1080/19420862.2025.2487604","DOIUrl":"https://doi.org/10.1080/19420862.2025.2487604","url":null,"abstract":"<p><p>The European Immunogenicity Platform (EIP) celebrated the 15th edition of its Open Symposium on Immunogenicity of Biopharmaceuticals and its associated one-day workshop on 22-24 February 2024 in Lisbon. The meeting attracted experts and newcomers across industry, regulatory agencies, and academia, who actively participated in 3 days of discussion on risk assessment, monitoring, and mitigation of unwanted immunogenicity of biologics. Besides oral presentations, poster sessions were held to maximize scientific exchange and networking opportunities. Therapeutic proteins and emerging gene and cell-based therapies present promising therapeutic options for addressing unmet medical needs or when conventional treatment approaches have failed. Nonetheless, the development of an immune response against these therapeutic agents is a significant concern, as it occurs in a considerable number of cases across various products and indications. The specific anti-drug antibodies that develop can lead to adverse safety events, inhibition of drug activity, or accelerated clearance, all of which result in a loss of treatment efficacy. The EIP serves as a forum for experts and newcomers in the immunogenicity field, fostering discussion among scientists from industry and academia, encouraging interactions with regulatory agencies, and disseminating knowledge and advancements in immunogenicity sciences to the broader scientific community. This report covers the main topics discussed during the EIP 15th Open Symposium on Immunogenicity of Biopharmaceuticals, and the one-day workshop on practical aspects of immunogenicity held prior to the conference. Key topics included immunogenicity testing, clinical relevance of immunogenicity, immunogenicity risk assessment and mitigation, and current regulatory considerations.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2487604"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequence-based engineering of pH-sensitive antibodies for tumor targeting or endosomal recycling applications.","authors":"Wanlei Wei,Traian Sulea","doi":"10.1080/19420862.2024.2404064","DOIUrl":"https://doi.org/10.1080/19420862.2024.2404064","url":null,"abstract":"The engineering of pH-sensitive therapeutic antibodies, particularly for improving effectiveness and specificity in acidic solid-tumor microenvironments, has recently gained traction. While there is a justified need for pH-dependent immunotherapies, current engineering techniques are tedious and laborious, requiring repeated rounds of experiments under different pH conditions. Inexpensive computational techniques to predict the effectiveness of His pH-switches require antibody-antigen complex structures, but these are lacking in most cases. To circumvent these requirements, we introduce a sequence-based in silico method for predicting His mutations in the variable region of antibodies, which could lead to pH-biased antigen binding. This method, called Sequence-based Identification of pH-sensitive Antibody Binding (SIpHAB), was trained on 3D-structure-based calculations of 3,490 antibody-antigen complexes with solved experimental structures. SIpHAB was parametrized to enhance preferential binding either toward or against the acidic pH, for selective targeting of solid tumors or for antigen release in the endosome, respectively. Applications to nine antibody-antigen systems with previously reported binding preferences at different pHs demonstrated the utility and enrichment capabilities of this high-throughput computational tool. SIpHAB, which only requires knowledge of the antibody primary amino-acid sequence, could enable a more efficient triage of pH-sensitive antibody candidates than could be achieved conventionally. An online webserver for running SipHAB is available freely at https://mm.nrc-cnrc.gc.ca/software/siphab/runner/.","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"4 1","pages":"2404064"},"PeriodicalIF":5.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors","authors":"Geoff Hale, Jelle De Vos, Alastair Douglas Davy, Koen Sandra, Ian Wilkinson","doi":"10.1080/19420862.2024.2402701","DOIUrl":"https://doi.org/10.1080/19420862.2024.2402701","url":null,"abstract":"Elimination of the binding of immunoglobulin Fc to Fc gamma receptors is highly desirable for the avoidance of unwanted inflammatory responses to therapeutic antibodies and fusion proteins. Many di...","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"1 1","pages":"2402701"},"PeriodicalIF":5.3,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating large-volume subcutaneous injections of biopharmaceuticals: a systematic review of clinical pipelines and approved products","authors":"Philip Green, Andreas Schneider, Jakob Lange","doi":"10.1080/19420862.2024.2402713","DOIUrl":"https://doi.org/10.1080/19420862.2024.2402713","url":null,"abstract":"Subcutaneous (SC) administration is transforming the delivery of biopharmaceuticals, facilitating care in a variety of healthcare settings, including home self-treatment. Large-volume single SC dos...","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"4 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody association in solution: cluster distributions and mechanisms","authors":"Sandi Brudar, Leonid Breydo, Elisha Chung, Ken A. Dill, Nasim Ehterami, Ketan Phadnis, Samir Senapati, Mohammed Shameem, Xiaolin Tang, Muhammmad Tayyab, Barbara Hribar-Lee","doi":"10.1080/19420862.2024.2339582","DOIUrl":"https://doi.org/10.1080/19420862.2024.2339582","url":null,"abstract":"Understanding factors that affect the clustering and association of antibodies molecules in solution is critical to their development as therapeutics. For 19 different monoclonal antibody (mAb) sol...","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"100 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing neonatal Fc receptor binding enhances clearance and brain-to-blood ratio of TfR-delivered bispecific amyloid-β antibody","authors":"Eva Schlein, Ken G. Andersson, Tiffany Dallas, Stina Syvänen, Dag Sehlin","doi":"10.1080/19420862.2024.2339337","DOIUrl":"https://doi.org/10.1080/19420862.2024.2339337","url":null,"abstract":"Recent development of amyloid-β (Aβ)-targeted immunotherapies for Alzheimer’s disease (AD) have highlighted the need for accurate diagnostic methods. Antibody-based positron emission tomography (PE...","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}